Intra- and inter-cortical motor excitability in Alzheimer’s disease

Abstract

Transcranial magnetic stimulation (TMS) provides evidence for facilitatory and inhibitory motor dysfunctions in Alzheimer's disease (AD). The corpus callosum (CC) is affected in AD already at early stages consistent with the hypothesis that AD patients exhibit alterations in transcallosally mediated motor inhibition (ipsilateral silent period, iSP). Therefore, here we aimed at investigating the integrity not only of intra-, but also of inter-hemispheric mechanisms of cortical motor excitability in AD. We determined the iSP, the resting motor threshold (RMT), and the amplitude of motor evoked potentials (MEP) in 19 AD patients and 19 healthy controls using single-pulse TMS. Furthermore, we used paired-pulse TMS to study the intra-cortical inhibition (ICI) and intra-cortical facilitation (ICF). All subjects underwent comprehensive neuropsychologic, clinical, and laboratory testing, and neuroimaging to exclude significant co-morbidity. In AD patients, the RMT was significantly reduced (Oneway-ANOVA). An analysis of covariance (ANCOVA) revealed a strong group specific interaction of the inhibitory interstimulus intervals (p = 0.005) with a reduced ICI in AD. Furthermore, we found a significantly prolonged iSP-latency (p = 0.003) in AD compared to controls, whereas the iSP-duration was not different. The iSP-latency correlated significantly with the ICI (ANCOVA) (p = 0.02). The ICF did not differ significantly between groups. Our data suggest comprehensive but still subclinical dysfunctions of motor cortical inhibition in mild to moderate clinical stages of AD with strong interactions of intra- and inter-hemispheric inhibitory phenomena. Future studies are needed to show the potential prognostic relevance of these findings for the further course of the disease.

Transcranial Magnetic Stimulation for the Assessment of Neurodegenerative Disease

“…Of further relevance, reduction of SICI in AD has been previously reported [170,171,173], and SICI was increased Fig. 4 Receiver-operator characteristic curve disclosed that averaged short-interval intracortical inhibition (SICI; between interstimulus interval 1-7 ms) is the most robust of the transcranial magnetic stimulation (TMS) outcome parameters in differentiating amyotrophic lateral sclerosis from mimicking diseases.…”

“…Namely, the motor thresholds appear significantly reduced in early stages of the disease, with an initial threshold reduction paralleling disease progression, despite pharmacological treatment [167][168][169][170][171]. In advanced disease, there is a gradual increase of motor thresholds, probably reflecting the underlying cortical neuronal degeneration [172].…”

Sensorimotor cortex excitability and connectivity in Alzheimer's disease: A TMS-EEG Co-registration study

“…However a contribution of the corpus callosum cannot be excluded. All these pathways are known to be functionally and structurally disrupted in AD [Hoeppner et al, ] with a clear involvement of the aforementioned balance between excitatory and inhibitory neurotransmission. On one hand the map analysis seems to suggest in AD patients rearranged cortico‐cortical connectivity between the premotor, motor and parietal cortices that are anatomically interconnected through distinct white matter tracts forming the superior longitudinal fasciculus (SLF).…”

Transcranial magnetic stimulation (TMS)/repetitive TMS in mild cognitive impairment and Alzheimer's disease

“…A consistent finding among TMS studies performed in patients with AD is the decreased RMT. Most of them found significantly reduced RMT in patients with AD compared with healthy controls , or a tendency toward a reduced RMT even if without statistically significant difference . Only one study noted no difference in RMT between patients with AD and controls , and one found increased RMT in AD .…”